This week exciting new research from a collaboration between Chinese researchers and scientists at the University of Iowa has pointed towards a clinically-available, generic drug that could be re-purposed for Parkinson’s.
The researchers found a drug called Terazosin – which is used for the treatment of enlarged prostates and high blood pressure – can boost energy production in neurons, and also rescue multiple preclinical models of Parkinson’s (including human cell cultures).
Most intriguing, however, was their discovery that people taking Terazosin (or similar drugs) have a reduced incidence of Parkinson’s, and people with Parkinson’s who take Terazosin seem to have less disease progression.
In today’s post, we will look at what Terazosin is, how it functions, what this new research suggests, and how the finding is being taken forward.
Reader questions. Source: Yoursalesplaybook
So I have had a few inquiries over the last 24 hours.
Lots of questions.
A wee bit of interest in some recent Parkinson’s associated research.
It seems that there was a bit of excitement generated by press releases regarding new research from a group of researchers in China and the University of Iowa suggesting that a commonly used blood pressure and prostate treatment called Terazosin not only had beneficial effects in multiple models of Parkinson’s, but also reduced the incidence of Parkinson’s in people taking the drug.
Terazosin. Source: Wikipedia
Here is the study in question:
Title: Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases.
Authors: Cai R, Zhang Y, Simmering JE, Schultz JL, Li Y, Fernandez-Carasa I, Consiglio A, Raya A, Polgreen PM, Narayanan NS, Yuan Y, Chen Z, Su W, Han Y, Zhao C, Gao L, Ji X, Welsh MJ, Liu L.
Journal: J Clin Invest. 2019 Sep 16. pii: 129987.
PMID: 31524631 (This report is OPEN ACCESS if you would like to read it)
In this study, the researchers investigated the properties of a drug called terazosin in various models of Parkinson’s.
What is terazosin?
The results of a clinical trial published this week not only provide further evidence that exercise has beneficial effects for people with Parkinson’s, but may also be disease modifying.
Researchers in the Netherlands recruited 130 people with Parkinson’s to take part in a study of clinical exercise. The participants were divided into 2 groups – one instructed to do aerobic exercise (an exergaming activity), while the other group was given stretching activities.
After 6 months, the investigators found that the symptoms of the aerobic exercise group had progressed at a slower rate than the other group, suggesting that the benefits of the exercise regime were clinically relevant.
In today’s post, we will review the study, discuss what exergaming is, and explore what may happen next.
A sweet ride. Source: Electricbikereview
I recently bought a bike (not the one above). Why? Because I need to get fit.
Honestly, I am so unfit at the moment. Due to a reconstructed foot, running is not an option. The gym and the pool are too expensive and time consuming (read: I’m cheap and lazy).
So I bought a bike, with the goal of getting out into the country side several times a week. And I have to say: I absolutely love it! The freedom of it has been smiling like an idiot, and reminiscing of a younger age when I was less beautiful.
But all kidding aside, cycling is a great way of keeping fit and there is some REALLY interesting Parkinson’s research being done on cycling at the moment.
What do you mean?
For the last 21 years, the protein alpha synuclein has developed a reputation as public enemy #1 in the world of Parkinson’s.
Tiny errors in the DNA that provides the instructions from making the alpha synuclein protein were found to be the first genetic risk factor for the condition, and then the protein itself was found to be present in Lewy bodies – one of the cardinal features of Parkinson’s in the brain.
In addition, animal models of Parkinson’s involving the production of high levels of alpha synuclein have demonstrated that this build up of protein can be neurotoxic, and it has been reported that alpha synuclein deposits can appear in cells that had been transplanted into the brains of people with the Parkinson’s.
But very recently a new theory (and supporting data) regarding this protein has been proposed, and it paints a slightly different picture.
In today’s post we will look at this new theory (and the provided data), and consider what this could mean for our efforts to therapeutically deal with Parkinson’s.
Ok, today’s post is diving straight into the science lesson.
No preamble, just good old cell biology.
In almost every cell in your body, there is a structure called the nucleus. It is rather critical to life as we know it, because the nucleus is the vault which holds the blue prints (aka DNA) for making and maintaining a copy of ‘you’.
The nucleus of a cell. Source: Biologywise
The nucleus is a very busy area of any cell as it provides the instructions for cellular function. At any point in the day or night, many regions of the DNA are continuously being read and converted in RNA (in a process called transcription).
While DNA is the blue print, RNA is the facsimile of a region of DNA that is used for making a particular protein. While DNA is precious, unique, and must be carefully guarded, the copied version (RNA) is readily disposable. Once produced (or transcribed), each piece of RNA will exit the nucleus and enter an adjoining structure called the endoplasmic reticulum. On a very basic level, the endoplasmic reticulum is where the RNA facsimile of the instructions is used to produce protein.
Making a protein. Source: Quora
Some of these newly formed proteins will be released outside of the cell (to send messages to other cells), while some other newly formed proteins will be transported to distant parts of the cell to do specific tasks. But another collection of the newly formed proteins will be shipped back to the nucleus where they will play important roles in maintaining, transcribing, monitoring, or repairing the precious DNA.
Recently published research suggests that the Parkinson’s associated protein alpha synuclein may have a function in the protection of DNA.
Specifically, it appears to be involved with DNA repair.
Remind me again: What is alpha synuclein?
A major focus on Parkinson’s research is inflammation.
Inflammation is a vital part of our immune system’s response to infection or injury. It is means by which the body signals to the cells of immune system that something might be wrong and help is required. It is a complex, multi-stage process, involving many different mechanisms which help to amplify and resolve the response.
Recently, some researchers reported some interesting data regarding the ‘resolving’ aspect of the inflammatory response in Parkinson’s. It involved a protein called Resolvin.
In today’s post, we will look at what Resolvin is, what the new research reported, and how this information could be useful in the development of future therapies for Parkinson’s.
Spot the unhealthy cell – exhibiting signs of stress (yellow). Source: Gettyimages
When cells in your body are stressed or sick, they begin to release tiny messenger proteins which inform the rest of your body that something is wrong.
When enough of these messenger proteins are released that the immune system becomes activated, it can cause inflammation.
What is inflammation?
Inflammation is a critical part of the immune system’s response to trouble. It is the body’s way of communicating to the immune system that something is wrong and activating it so that it can help deal with the situation.
By releasing the messenger proteins (called cytokines), injured/sick cells kick off a process that results in multiple types of immune cells entering the troubled area of the body and undertaking very specific tasks.
The inflammatory process. Source: Trainingcor
The strength of the immune response depends on the volume of the signal arising from those released messenger proteins. And there are processes that can amplify the immune response.
But an important component of the immune response that is often overlooked is resolution.
Once an infection/injury has been dealt with, the immune response must be resolved. And there are tiny messenger proteins that our body producing naturally which involved in dampening down the immune response. They are typically released when a situation has been resolved.
One group of resolving messenger proteins are called Resolvins.
What are Resolvins?
New data from researchers in Taiwan has intriguing implications for our understanding of the development of Parkinson’s.
An analysis of the enormous national medical database pointed towards towards hepatitis C viral infections as a risk factor for developing Parkinson’s.
But here is the twist in the tale: Interferon-based antiviral therapy reduces that risk back to normal.
In today’s post, we will review the new research, discuss what interferons are, explore what other research has been conducted on interferons in the context of Parkinson’s, and consider the implications of this new research for Parkinson’s.
We have learnt a great deal about Parkinson’s over the last few years via the use of “big data”.
Whether it be the analysis of vast pools of genetic information collected from tens of thousands of individuals with the condition, to analysing massive datasets of longitudinal medical information, these investigations has open new avenues of research and investigation.
For example, “big data” studies have demonstrated that those who smoke cigarettes and drink coffee have a reduced chance of developing Parkinson’s (click here to read a previous SoPD post on this topic). ‘Big data studies have also pointed towards novel therapeutic approaches (click here for a previous SoPD post highighting an example).
Recently, an analysis of medical records from Taiwan have shed new light on another potential influencer of Parkinson’s risk: Hepatitis C
What is Hepatitis C?
At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during August 2019.
The post is divided into seven parts based on the type of research:
So, what happened during August 2019?
In world news:
7th August – Scientists discovered that staring at seagulls can stop them from stealing food (Click here to read more about this – no, really, this is serious science).
14th August – Swedish climate activist, 16 year old Greta Thunberg set sail across the Atlantic ocean in a zero-carbon yacht – almost one year after she started her school strike for the climate protest on 20 August – to attend various meetings in the US (Click here to read more about this).
23rd August – At the G7 meeting, Western countries (who have utterly deforested themselves in the name of commerce) decried the burning of the Amazon rain forest (which does NOT contain 20% of the world’s oxygen – click here to read more about that), rather than simply proposing to re-foresting themselves (Click here to read more about this).
27th August – American rocket company SpaceX conducted a successful flight of their “Starhopper” craft. Starhopper is an early test prototype of SpaceX’s Mars-colonizing Starship spacecraft (Click here to read more about this)
28th August – Greta arrived in New York (Click here to read more about this).
In the world of Parkinson’s research, a great deal of new research and news was reported:
In August 2019, there were 924 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (5688 for all of 2019 so far). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).
The top 5 pieces of Parkinson’s news
The immune system is our main line of defense against a world full of potentially dangerous disease causing agents. It is a complicated beast that does a fantastic job of keeping us safe and well.
Recently, however, there was an interesting study suggesting that a genetic risk factor for Parkinson’s may be associated with an over-reaction from the immune system in response to infection from a common human food poisoning bug.
Specifically, mice who were missing the gene PINK1 literally had an ‘autoimmune reaction’ to the infection – that is the immune system began attacking healthy cells of the body – while normal mice (with intact PINK1 genes) recovered from the infection and went about their business.
In today’s post, we will explore this new research and discuss why we may need to rethink PINK.
Source: Huffington Post
I have had a guts full of all this gut research being published about Parkinson’s.
[NOTE 1.: For the unitiated: A “guts full” – Adjective, Kiwi colloquialism. Meaning ‘Had enough of’, ‘fed up of’, ‘endured to the point of tolerance’]
[NOTE 2.: The author of this blog is a Kiwi]
I really can’t stomach anymore of it.
And my gut feeling suggests that there is only more to come. It would be nice though, to have something else… something different to digest.
So what is today’s post all about?
Gut research of course.
But this gut research has a REALLY interesting twist.
Increasing preclinical evidence is being presented that suggests the gastrointestinal system can play a role in models of Parkinson’s. In addition, there is mounting epidemiological data indicating that the gut can have some kind of influence in people with the condition.
Recently, a new paper was published which explores the involvement of the vagus nerve. This is the bundle of nerves connecting the gut to the brain.
Specifically, the researchers cut the vagus nerve in mice who had the Parkinson’s associated protein alpha synuclein introduced to their guts, and they found that these mice did not develop the characteristics of Parkinson’s, while those mice with intact vagus nerves did.
In today’s post, we will discuss this new report, review some of the additional preclinical and epidemiological data, and try to understand what it all means for our understanding of Parkinson’s.
Today’s post is about the origin of things. Specifically, Parkinson’s.
But we will begins with words: Consider for a moment the title of this post: Viva las vagus.
When most people read of the word ‘Viva‘, they think of it as a call to cheer or applaud somthing (for example: “Vive la France!” or “Viva las Vegas”), but the origin of the word has a slightly different meaning.
Viva is a shortening of the Latin term viva voce, meaning “live voice”. And in this context it refers to an oral examination – typically for an academic qualification. For example, a European PhD examination is referred to as “viva” and it is an oral denfense (sometimes public – eek!) of the thesis.
A PhD viva examination. Source: Guardian
‘Las’ is simply the Spanish word for ‘the’. And the word ‘vagus’ originates from the Latin, meaning ‘wandering, uncertain’.
Thus, the title of today’s post could – in effect – be “an examination of the uncertain”.
In anatomy and medicine the word, Vagus also refers to an important part of our nervous system.
Cell replacement therapy is a key component of any “cure” for Parkinson’s – replacing the cells that have been lost over the course of the condition.
Cell transplantation of dopamine neurons has a long track record of both preclinical and clinical development and represents the most developed of the cell replacement approaches.
Two weeks ago, the biotech firm BlueRock Therapeutics announced an agreement under which the pharmaceutical company Bayer AG would fully acquire the company.
In today’s post we will discuss why this is major news for the Parkinson’s community and an important development for the field of cell replacement therapy.
On the 8th August, Bayer AG and BlueRock Therapeutics announced an agreement under which Bayer will “fully acquire BlueRock Therapeutics, a privately held US-headquartered biotechnology company focused on developing engineered cell therapies in the fields of neurology, cardiology and immunology, using a proprietary induced pluripotent stem cell (iPSC) platform” (Source).
What is BlueRock Therapeutics?
Versant Ventures is a leading venture capital firm that specializes in investing “in game changing biopharmaceuticals, medical devices, and other life science opportunities”. Leaps by Bayer is an effort by the Pharmaceutical company Bayer at “spearheading a movement to make paradigm-shifting advances in the life sciences – targeting the breakthroughs that could fundamentally change the world for the better”.
The news on the 8th August means Bayer will acquire the remaining stake for approximately US$240 million in cash (to be paid upfront) and an additional US$360 million which will be payable upon the achievement of certain pre-defined development milestones.
Given that Bayer currently holds 40.8% stake in BlueRock Therapeutics, this announcement values the company at approximately US$1 billion.
Interesting, but what exactly does BlueRock do?
Recently it has been determined that many people with Parkinson’s have a distinct smell. It is a subtle odour that only some individuals with a very sensitive sense of smell can detect (Click here to read a previous SoPD post on this topic).
This curious discovery has given rise to a number of interesting research programmes which are trying to determine the underlying biology of the odour and how this knowledge could be useful in early detection of the condition and in our understanding of the disease.
In addition, there has been efforts to train dogs to detect the smell of Parkinson’s, and recently I was invited to visit a research centre that is teaching dogs to differentiate between odours, and identify the odour from people with Parkinson’s. It was a wonderful experience.
In today’s post, we will look at what the Medical Detection Dogs does and what implications their research could have for Parkinson’s.
In my role of Deputy Director at the Cure Parkinson’s Trust I get invited to visit many interesting research efforts associated with Parkinson’s.
But recently there was one visit that I was particularly looking forward to.
A couple of weeks ago I drove up to Milton Keynes here in the UK and visited a charity called Medical Detection Dogs.
What do they do?